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Antimicrob Agents Chemother. 2017 Jul 25;61(8). pii: e00315-17. doi: 10.1128/AAC.00315-17. Print 2017 Aug.

Impact of HIV-1 Integrase L74F and V75I Mutations in a Clinical Isolate on Resistance to Second-Generation Integrase Strand Transfer Inhibitors.

Author information

1
Department of Infectious Disease and Immunology, Clinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya, Aichi, Japan atsuko.hachiya@nnh.go.jp.
2
Division of Biological Information Analysis, Clinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya, Aichi, Japan.
3
Christopher S. Bond Life Sciences Center, Department of Molecular Microbiology and Immunology, University of Missouri School of Medicine, Columbia, Missouri, USA.
4
Department of Infectious Disease and Immunology, Clinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya, Aichi, Japan.
5
Department of Biochemistry, University of Missouri, Columbia, Missouri, USA.
6
Department of AIDS Research, Graduated School of Medicine Nagoya University, Nagoya, Aichi, Japan.

Abstract

A novel HIV-1 integrase mutation pattern, L74F V75I, which conferred resistance to first-generation integrase strand transfer inhibitors (INSTIs), was identified in a clinical case with virological failure under a raltegravir-based regimen. Addition of L74F V75I to N155H or G140S Q148H increased resistance levels to the second-generation INSTIs dolutegravir (>385- and 100-fold, respectively) and cabotegravir (153- and 197-fold, respectively). These findings are important for the development of an accurate system for interpretation of INSTI resistance and the rational design of next-generation INSTIs.

KEYWORDS:

dolutegravir; drug resistance mechanisms; human immunodeficiency virus; integrase; integrase strand transfer inhibitor

PMID:
28533248
PMCID:
PMC5527620
DOI:
10.1128/AAC.00315-17
[Indexed for MEDLINE]
Free PMC Article

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